Related Experiment Video
Updated: Jun 16, 2026
09:34
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Worldwide distribution of PSEN1 Met146Leu mutation: a large variability for a founder mutation
A C Bruni1, L Bernardi, R Colao
1Centro Regionale di Neurogenetica, Azienda Sanitaria Provinciale Catanzaro, Viale A. Perugini, 88046 Lamezia Terme (CZ), Italy. bruni@arn.it
Neurology
|February 19, 2010
Summary
Global familial Alzheimer disease (FAD) families with the PSEN1 Met146Leu mutation share a common Southern Italian ancestor. This mutation causes varied early-onset FAD symptoms, including memory loss and frontal impairment.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Familial Alzheimer disease (FAD) provides insights into clinical variability of presenilin 1 (PSEN1) mutations.
- Two Calabrian early-onset FAD (EOFAD) families with the PSEN1 Met146Leu mutation were identified, suggesting a common ancestral origin.
Observation:
- EOFAD Met146Leu families worldwide were traced to a single kindred originating from Southern Italy before the 17th century.
- Phenotypic variability at onset was broad, with four distinct clinical presentations observed in 50 patients.
Findings:
- The PSEN1 Met146Leu mutation is linked to a single, geographically widespread kindred.
- Clinical presentations included classic Alzheimer disease symptoms and frontal impairment, potentially linked to specific prefrontal cortex dysfunction.
Implications:
- The PSEN1 Met146Leu mutation's origin in Southern Italy highlights founder effects in EOFAD.
- Varied clinical presentations suggest differential cortical area involvement in early Alzheimer pathology.
- Despite phenotypic diversity, the underlying neurodegeneration is unequivocally Alzheimer's disease.
Related Concept Videos
02:26Comparing Copy Number Variations and SNPs
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
01:05Single Nucleotide Polymorphisms-SNPs
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
01:30Point and Frameshift Mutations
Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...
01:39Mutations
Overview
01:43Incomplete Dominance
Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.
01:27Principles of Pharmacogenetics: Types of Genetic Variants
The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...